In this issue

ovarian cancer and serve as a promising target for new treatments.


SCD1 inhibition enhances the ef fec tor func tions of CD8+ T cells via AC AT1-dependent reduc tion of es terif ied choles terol
Immunotherapy is a type of cancer treatment that uses the body's own immune system to fight cancer.It is less toxic compared to other cancer treatments.However, it is not effective on all cancer patients and its effects depend on the immune environment around the tumor.Therefore, it is important to study and develop new immunotherapy strategies.
Previous studies have shown that inhibition of the enzymes stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA acetyltransferase 1 (ACAT1) improves the immune system's ability to fight cancer.
These enzymes play an important role in fat and cholesterol metabolism, respectively.The enzyme SCD1 helps in production of a fatty acid called oleic acid and ACATI converts oleic acid to esterified cholesterol.These enzymes are known to significantly influence immune cell performance.
However, the underlying process through which inhibitors of these enzymes enhance the function of immune cells is unknown.
Researchers have now identified the relation between SCD1 and ACAT1 and the novel mechanism through which the inhibitors of these enzymes improve the function of CD8 + T cells.CD8 + T cells are a type of immune cells that produce chemicals called cytokines to eliminate tumor cells.
The researchers studied the effects of enzyme inhibitors on lab-cultured cells and in tumor-bearing mice.They observed that inhibition of SCD1 resulted in decrease in oleic acid and esterified cholesterol produced by ACAT1.This in turn enhanced the ability of CD8 + T cells to destroy cancer cells due to increased production of a cytokine called interferon gamma (INFγ).
These findings indicate that SCD1 inhibitors and ACAT1 inhibitors together can improve the function of immune cells to eliminate cancer cells.Thus, SCD1 and ACAT1 inhibitors can be used as drugs for cancer immunotherapy.Moreover, the SCD1 and ACAT1 pathways can be targeted to increase the effectiveness of immunotherapy.The researchers attributed the mechanistic anticancer activity of the TβRI-TβRII-Fc protein to its ability to disrupt the production of regulatory proteins in the TME.These proteins-which include heparinbinding epidermal growth factor-like growth factor (HB-EGF), interleukin-1β (IL-1β), and epiregulin (EREG)-help cancer cells divide uncontrollably and increase blood vessel formation to support their growth.
In summary, introduction of TβRI-TβRII-Fc receptors disrupts TGFβ signaling in the TME by deactivating the HB-EGF/IL-1β/EREG pathways.This suggests that the TβRI-TβRII-Fc protein could potentially be used to target the TME of cancer cells and improve the treatment outcomes for patients with cancer.https:// doi.org/ 10. 1111/ cas.16006 Not published yet https://onlinelibrary.wiley.com/doi/full/10.1111/CAS.15999Inhibition of TG Fβ signals suppresses tumor formation by regulation of tumor microenvironment net work s Cancer, disease characterized by cells that grow and divide in an uncoordinated, abnormal fashion, continues to have a very high global death rate despite the availability of multiple treatment strategies.Many anticancer medications exhibit sub-optimal effectiveness owing to the complexity of the tumor microenvironment (TME, a region surrounding the cancer cells).The TME consists of cancer cells, connective tissue called stroma, and numerous blood vessels, which collectively support tumor growth.The presence of transforming growth factorβ (TGFβ) in the TME, too, plays an important role in tumor growth.TGFβ stimulates tumor angiogenesis-the formation of blood vessels in the stroma-and facilitates epithelial-mesenchymal transition (EMT), a process that allows cancer cells to transition from being epithelial cells (or outer layer cells) into mesenchymal cells (which form the connective tissue), thus allowing them to migrate to other parts of the body and bolstering their metastatic potential.In this study, Tokizaki et al. studied the anticancer activity of the TβRI-TβRII-Fc receptor protein they had previously developed.These receptor proteins can trap and block TGFβ in the TME.Their findings showed that the TβRI-TβRII-Fc protein arrested EMT transition in lab-cultured oral cancer cells.It also effectively suppressed tumor growth in mice.